The overall objective of this research project continues to be to elucidate mechanisms accounting for the relative insensitivity of neoplastic tissues to hormonal and nutritional stimuli, to determine the adaptive mechanisms which permit tumors to proliferate despite vitamin deficiency in the host, and to utilize experimental tumors in animals to provide insights into the pathogenesis of cachexia and malnutrition in patients with cancer. The major studies in progress along these lines are as follows: (a) Riboflavin excretion and turnover in a unusual case of multiple myeloma, who has a monoclonal IgG lambda that binds riboflavin with high specificity. An enormous delay in the turnover and excretion of vitamin B2 was demonstrated. (b) Thyroid hormonal regulation of L-triiodothyronine aminotransferase activity in normal and neoplastic liver. In rats bearing Novikoff hepatoma grown intraperitoneally, triiodothyronine in large doses increases enzyme activity in liver but not in tumor tissue. (c) Hormonal control of flavin metabolism. Thyroid hormones enhance the overall rates of incorporation of riboflavin into flavins bound covalently to tissue proteins in liver, cerebellum and cerebrum. (d) Abnormalities in taste and smell sensations in clinical and experimental hypothyroidism. Defects of taste and smell have been observed in the majority of hypothyroid patients and are largely reversible with treatment. In rats rendered hypothyroid with radioactive iodine, abnormal taste preferences are also demonstrable, and provide a useful animal model with which to study taste sensations in endocrine and neoplastic disorders.